Altered Levels and Regulation of Stathmin in Paclitaxel-Resistant Ovarian Cancer Cells

Oncogene. 2003 Dec 4;22(55):8924-30. doi: 10.1038/sj.onc.1207060.

Abstract

Two paclitaxel(Ptx)-resistant ovarian cancer cell lines, 1A9/Ptx-10 and 1A9/Ptx-22, isolated from the 1A9 cell line (a clone of the A2780 line) by continuous exposure to Ptx and verapamil, have point mutations in their major beta-tubulin gene and in one or both alleles of their TP53 gene. These cells were examined for alterations in cell cycle regulators and the tubulin-binding protein stathmin. Unlike parental cells, neither 1A9/Ptx-10 nor 1A9/Ptx-22 expressed detectable levels of p21(WAF1/Cip1), a putative transcriptional regulator of stathmin, but did overexpress stathmin and Bcl2. No differences were noted in the expression levels of proliferative cell nuclear antigen or tyrosine-phosphorylated p34Cdc2. Ptx treatment altered little the expression of stathmin in the parental cell line, although it increased p21(WAF1/Cip1) levels several-fold. Infection of Ptx-resistant lines with a wild-type TP53-bearing adenovirus (AdWTp53) changed cell cycle distribution and increased the levels of p21(WAF1/Cip1), but caused no changes in stathmin levels. Microtubule drug resistance in ovarian carcinoma may be associated with altered p53/21(WAF1/Cip1) regulatory pathways for stathmin expression and function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Microtubule Proteins*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Paclitaxel / pharmacology
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / genetics*
  • Stathmin

Substances

  • Antineoplastic Agents, Phytogenic
  • Microtubule Proteins
  • Phosphoproteins
  • STMN1 protein, human
  • Stathmin
  • Paclitaxel